Please use this identifier to cite or link to this item:
https://doi.org/10.1038/s41467-022-28533-z
DC Field | Value | |
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dc.title | Pharmacological perturbation of CXCL1 signaling alleviates neuropathogenesis in a model of HEVA71 infection | |
dc.contributor.author | SARAVANAN S/O GUNASEELAN | |
dc.contributor.author | Mohammed Zacky Ariffin | |
dc.contributor.author | SANJAY KHANNA | |
dc.contributor.author | Ooi, MH | |
dc.contributor.author | Perera, D | |
dc.contributor.author | Chu, J.J.H. | |
dc.contributor.author | Chua J.J.E. | |
dc.date.accessioned | 2022-03-02T07:16:26Z | |
dc.date.available | 2022-03-02T07:16:26Z | |
dc.date.issued | 2022-02-16 | |
dc.identifier.citation | SARAVANAN S/O GUNASEELAN, Mohammed Zacky Ariffin, SANJAY KHANNA, Ooi, MH, Perera, D, Chu, J.J.H., Chua J.J.E. (2022-02-16). Pharmacological perturbation of CXCL1 signaling alleviates neuropathogenesis in a model of HEVA71 infection. Nature communications 13 (1) : 890-. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-022-28533-z | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/216616 | |
dc.description.abstract | Hand, foot and mouth disease (HFMD) caused by Human Enterovirus A71 (HEVA71) infection is typically a benign infection. However, in minority of cases, children can develop severe neuropathology that culminate in fatality. Approximately 36.9% of HEVA71-related hospitalizations develop neurological complications, of which 10.5% are fatal. Yet, the mechanism by which HEVA71 induces these neurological deficits remain unclear. Here, we show that HEVA71-infected astrocytes release CXCL1 which supports viral replication in neurons by activating the CXCR2 receptor-associated ERK1/2 signaling pathway. Elevated CXCL1 levels correlates with disease severity in a HEVA71-infected mice model. In humans infected with HEVA71, high CXCL1 levels are only present in patients presenting neurological complications. CXCL1 release is specifically triggered by VP4 synthesis in HEVA71-infected astrocytes, which then acts via its receptor CXCR2 to enhance viral replication in neurons. Perturbing CXCL1 signaling or VP4 myristylation strongly attenuates viral replication. Treatment with AZD5069, a CXCL1-specific competitor, improves survival and lessens disease severity in infected animals. Collectively, these results highlight the CXCL1-CXCR2 signaling pathway as a potential target against HFMD neuropathogenesis. | |
dc.publisher | Springer Science and Business Media LLC | |
dc.source | Elements | |
dc.type | Article | |
dc.date.updated | 2022-03-02T05:31:23Z | |
dc.contributor.department | MICROBIOLOGY AND IMMUNOLOGY | |
dc.contributor.department | PHYSIOLOGY | |
dc.description.doi | 10.1038/s41467-022-28533-z | |
dc.description.sourcetitle | Nature communications | |
dc.description.volume | 13 | |
dc.description.issue | 1 | |
dc.description.page | 890- | |
dc.published.state | Published | |
Appears in Collections: | Staff Publications Elements |
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s41467-022-28533-z.pdf | Published version | 5.59 MB | Adobe PDF | OPEN | Published | View/Download |
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